Aging in cells

Description

In the aging brain, things just slow down. Enzymes that synthesize
neurotransmitters become less active.
Neurogenesis decreases.
Vesicules
become less efficient. The myelin
sheath changes composition, affecting the transmission of electrical
signals.

Up to 20% of some parts of the
hippocampus, which is involved with emotion and learning, may be lost.

Within the neuron, the protoplasm outside the nucleus can start to fill with
helical protein filaments known as
neurofibrillary tangles, which impact normal cell functioning and contribute to such as
Alzheimer's disease.

Many cells in the body normally reproduce by dividing. Cellular senescence or replicative
senescence is the phenomenon whereby cells stop dividing, typically after
about 50 divisions. Senescent cells are usually larger, with bigger nuclei.

In the brain, neurons cannot replicate but supporting cells such as
glia (which do replicate) help repair
brain damage. When these cells cannot replicate then brain decay can occur.

As cells divide, DNA telomeres (the looped
region of repetitive DNA at the end of chromosomes) shorten. This is believed to
limit the number of replications. Some cells, including stem cells and their
progeny, avoid this problem by using the enzyme telemerase to add new
repeats to the chromosome ends.

Other factors that lead to senescence include chromatin decondensation, DNA
damage, oncogene activation and over-activation of mitogenic stimuli.
Accumulation of mutations in somatic cells can also lead to senescence.

Apoptosis is the process of programmed cell death (as opposed to
necrosis and injury-related traumatic cell death). Between 50 and 70 billion
adult cells die each day (for children between 8 and 14 it is between 20 and 30
billion). It naturally happens when the cell is damaged somehow, is infected or
is stressed somehow.

Cells also divide and reproduce, keeping the system in overall balance,
although this happens much less in the brain (although there is some
neurogenesis).

Apoptosis is also a defense again cancer, preventing replication of damaged
cells. The decision for apoptosis comes from the cell itself, the surrounding
tissue or the immune system.

Network theory

There are various theories about the detail of cellular aging. Kowald and
Kirkwood's (1996) Network Theory takes the broad view that aging is a
combination of multiple factors.

Free radicals

Free radicals are any substance that have unpaired electrons and are
thus thermodynamically unstable and very reactive. In cells they react with
proteins, nucleic acids and (particularly) lipids, damaging the cell and its
membrane.

Animal experiments have shown that reducing free radicals increases
longevity. This has sparked a whole diet and health industry.

During transport to the inner mitochondrial membrane, oxygen molecules gain
four electrons, leading to the creation of superoxide radicals. Some of these
are converted to hydrogen peroxide, H2O2 which diffuses
through cell walls and generates more free radicals, in particular the hydroxyl
radical, HO•.

Oxygen-based free radicals plus non-radical oxidants (such as hydrogen
peroxide) are called reactive oxygen
species (ROS). These can also be caused by environmental pollution and
radiation, as well as internal cell effects. Nitric oxide and peroxynitrate are
reactive nitrogen species(RNS)
as well as ROS. RNS reacts with amino acids, thus disrupting function.

Adenosine
triphosphate (ATP) is produced as an energy source during the photosynthesis
and cellular respiration and is consumed by many enzymes and many cellular
processes. During its generation, electrons are transferred from reduced
coenzymes to oxygen. Between 1 and 5% of this production escapes and results in
the production of free radicals.

Redox, short for reduction-oxidation is the
process whereby an atom has its oxidation number
(the number of extra/reduced electrons) changed.
Oxidation is the loss of electrons, whilst reduction is a gain in
electrons.

Oxidative stressis an increased level
of free radicals and comes from an imbalance between the production of reactive
oxygen and the body's ability to detoxify the reactive intermediaries or repair
resulting damage.

Cells also have defense mechanisms to combat oxidative damage, with antioxidants including vitamins A and E,
glutathione (GSH), superoxide dismutase (SOD), catalyse and
glutathione peroxidase.